Rejuvesol

Rejuvesol® Red Blood Cell Processing Solution (Rejuvesol® Solution) is a sterile, non-pyrogenic solution of sodium pyruvate, inosine, adenine, dibasic sodium phosphate, and monobasic sodium phosphate in water for injection intended only for use in the extracorporeal rejuvenation of a unit of red blood cell concentrate (RBC). Each 50 mL of Rejuvesol® Solution contains sodium pyruvate 0.550 g, inosine 1.34 g, adenine 0.034 g, dibasic sodium phosphate (heptahydrate) 0.730 g, and monobasic sodium phosphate (monohydrate) 0.311 g, in water for injection, pH 6.7-7.4.

Rejuvesol® Solution is intended only for the extracorporeal rejuvenation of a RBC. It should never be directly administered to Humans.

Rejuvesol® Solution must not be added to whole blood because the additional plasma may reduce the effectiveness of the rejuvenation process. Immediately after rejuvenation, RBC must either be washed via an approved protocol prior to transfusion or glycerolized and frozen. RBC which have been rejuvenated, glycerolized, and frozen must be deglycerolized via an approved protocol prior to transfusion.

RBC rejuvenated before 6 days of storage may achieve 2,3-DPG levels in excess of 2 times normal and ATP levels in excess of 1.5 times normal.5,6 In patients with reduced arterial blood p02 of less than 40 torr, the use of RBC rejuvenated before 6 days of storage are contraindicated because their high 2,3-DPG levels and low oxygen affinity may impair proper oxygenation of the red blood cells in the lung.7

Rejuvenated RBC are further processed prior to transfusion to remove the un-used portion of Rejuvesol® Solution, by-products of the rejuvenation process, and any other potential storage-related impurities in Rejuvesol® Solution. Based on the concentration of the residual inosine in rejuvenated RBC that are either washed or deglycerolized, the average washout of inosine was calculated to be > 97.4%. A literature search for potential toxicity associated with the ingredients that comprise Rejuvesol® Solution, including potential metabolites, was conducted.23 This report concludes that no theoretical contraindications would be associated with the transfusion of a single unit of unwashed, rejuvenated RBC that would contain amounts of pyruvate, inosine, adenine, phosphate, hypoxanthine, uric acid, and lactate that exceed reference values (excluding lactate) as these substances are naturally metabolized and/or are excreted.23

The maximum number of properly processed rejuvenated RBC that can be transfused to a single recipient over their entire lifetime has not been determined.

It is recommended that the product be stored at 15 - 25 °C (59 - 77 °F). Protect from freezing. Exposure to temperatures near or below freezing may produce a white precipitate in the solution; this precipitate will dissolve upon brief incubation at room temperature. Alternatively, the product may be warmed at 37 °C for up to one hour in a dry air incubator to dissolve the precipitate.

NOTE: One 50 mL vial of Rejuvesol® Solution can be used to rejuvenate one unit of RBC derived from 450 mL, or the volume as stated in the package insert for the 800 mL primary collection bag, of whole blood when collected in an 800 mL primary collection bag.

MATERIALS AND EQUIPMENT

(As Suggested or Equivalent)

1. Temperature-controlled (circulating) water bath (Blue-M MW-1140A, Helmer DH-4).
2. Integral tubing sealer (Sebra 1100).
3. Alcohol swabs (70%) (B-D 6894).
4. One vial (50 mL) of Rejuvesol Red Blood Cell Processing Solution, Rejuvesol® Solution (Citra PN 7012).
5. Tubing set for the addition of Rejuvesol® Solution and glycerol solution - Rejuvenation Harness 28" (71 cm), MedSep, Corp. Code #980-52 or Y-type transfer set, Baxter International #4C1921 or equivalent.
6. Two watertight plastic overwrap bags (Kapak, Scotchpack, 404).
7. Waterproof tape (3M R202).
8. Overwrap bag impulse sealer (Stericon 210X).
9. Filtered airway needle (BD 5200) (Used only with Baxter International #4C1921).

PROCEDURE

I. TO COMBINE Rejuvesol® Solution WITH THE RBC7

1. Remove the flip-off protective cap from the Rejuvesol® Solution vial and swab the exposed rubber stopper surface with an alcohol swab.
2. Close all clamps.
3. Aseptically insert the appropriate spike or needle of the tubing set through the rubber stopper of the vial of Rejuvesol® Solution.
4. Aseptically insert the bag spike of the tubing set into the adaptor port on the integral tubing of the primary collection bag.
5. Elevate the Rejuvesol® Solution vial 28 inches above the primary collection bag.
6. If a drip chamber is on the tubing set, squeeze the drip chamber to prime the system and open the clamp of the tubing set. If there is no drip chamber on the tubing set, open the clamp and aseptically insert a filtered airway needle through the rubber stopper of the vial of Rejuvesol® Solution.
7. Allow the entire contents of the Rejuvesol® Solution to flow into the primary collection bag while gently agitating the mixture. This typically takes between 15 and 30 seconds.
8. After all of the Rejuvesol® Solution has been transferred, close the clamp and heat seal the tubing three times between the portion of the tubing set that connects the Rejuvesol® Solution vial to the Y-connector so that the unused vented spike remains attached to the adaptor port.
9. Cut the middle heat seal and discard the used tubing and empty Rejuvesol® Solution vial.
10. Proceed immediately to Section II.

II. TO INCUBATE THE RED BLOOD CELL/Rejuvesol® Solution MIXTURE FOR 60 MINUTES AT 37 °C1,7,10,11

NOTE: The timing of the incubation is measured from the time the red blood cell/Rejuvesol® Solution mixture is introduced into the water bath. The actual temperature of the red blood cell/Rejuvesol® Solution mixture does not reach 37 °C (the final temperature is usually 29-31 °C).

1. Place the primary collection bag containing the red blood cell/Rejuvesol® Solution mixture into a plastic overwrap bag with the unused portion of the Rejuvenation Harness or Y-type Transfer Set and flatten the overwrap to remove all air prior to sealing.
2. Seal the plastic bag with tape or heat seal.
3. Place the sealed overwrapped unit inside a second overwrap bag containing lead weights (to keep the unit submerged during incubation); flatten and seal.
4. Place the overwrapped unit in the water bath. Secure the overwrap bag to the inside wall of the water bath with waterproof tape.
5. Incubate the unit in a 37 °C water bath for 60 minutes.
6. Remove the overwrapped unit from the water bath; dry the outer overwrap bag with clean, disposable toweling and carefully remove the plastic overwraps from the red blood cell/Rejuvesol® Solution mixture assuring that the primary collection bag and mixture are not contaminated with any water from the water bath.

NOTE: Centrifugation after rejuvenation is not required for RBC intended to be frozen in the 800 mL Primary Collection Bag. Glycerolized RBC are centrifuged prior to freezing.

III. TO PROCESS THE RED BLOOD CELL/Rejuvesol® Solution MIXTURE AFTER INCUBATION7

1. After the 60 minute incubation at 37 °C, the red blood cell/Rejuvesol® Solution mixture is ready for immediate glycerolization.
2. Complete the glycerolization per Standard Operating Procedure. 7

NOTES:

i. Rejuvenated-glycerolized RBC to be frozen in the 800 mL primary collection bag must be concentrated to achieve a hematocrit of approximately 60 ± 5 % after glycerolization per Standard Operating Procedure.7 ii. No more than four (4) hours should elapse between the time the unit is removed from the refrigerator and the time the cells are placed in the freezer.11 iii. Rejuvenated-deglycerolized RBC not intended for immediate use should be resuspended in 0.9% Sodium Chloride, 0.2% Dextrose for storage at 1-6 °C. Then, just prior to use, to ensure < 1% hemolysis in the final product, concentrate the RBC following local SOP proven to achieve a hematocrit of approximately 85%.7,9,24

NOTE: REJUVENATED RBC STORED IN ANY OTHER ANTICOAGULANT/ADDITIVE SOLUTION COMBINATION HAVE NOT BEEN APPROVED FOR CRYOPRESERVATION.

MATERIALS AND EQUIPMENT

(As Suggested or Equivalent)

1. Temperature-controlled (circulating) water bath (Blue-M MW-1140A, Helmer DH-4).
2. Integral tubing sealer (Sebra 1100)
3. Alcohol swabs (70%) (B-D 6894).
4. One vial (50 mL) of Rejuvesol® Red Blood Cell Processing Solution, Rejuvesol® Solution (Citra PN 7012).
5. Y-type Rejuvenation Set for the addition of Rejuvesol® Solution (Citra PN 7212) or equivalent.
6. Two watertight plastic overwrap bags (Kapak, Scotchpack, 404).
7. Waterproof tape (3M R202).
8. Overwrap bag impulse sealer (Stericon 210X).

PROCEDURE

I. TO COMBINE Rejuvesol® Solution WITH THE RBC

1. Remove the flip-off protective cap from the Rejuvesol® Solution vial and swab the exposed rubber stopper surface with an alcohol swab.
2. Close all slide clamps of the Y-type Rejuvenation Set (Citra PN 7212).
3. Aseptically, insert the vented spike of the Y-type Rejuvenation Set into the stopper of the vial of Rejuvesol® Solution.
4. Join the tubing of the Y-type Rejuvenation Set to the integral tubing of the primary collection bag using a sterile docking device. Alternately, aseptically insert the bag spike of the Y-type Rejuvenation Set into one of the administration ports of the primary collection bag.
5. Elevate the Rejuvesol® Solution vial approximately 28 inches above the primary collection bag.
6. Squeeze the drip chamber to prime the system and open the slide clamp of the Y-type Rejuvenation Set.
7. Allow the entire contents of the Rejuvesol® Solution vial to flow into the primary bag while gently agitating the mixture. This typically takes between 15 and 30 seconds.
8. After all of the Rejuvesol® Solution has been transferred, close the slide clamp and heat seal the tubing three times between the portion of the Y-type Rejuvenation Set that connects the Rejuvesol® Solution vial to the primary collection bag.
9. Cut the middle heat seal and discard the used tubing and empty Rejuvesol® Solution vial.
10. Proceed immediately to Section II.

II. TO INCUBATE THE RED BLOOD CELL/Rejuvesol® Solution MIXTURE FOR 60 MINUTES AT 37 °C1,8,9,11,13

NOTE: The timing of the incubation is measured from the time the red blood cell/Rejuvesol® Solution mixture is introduced into the water bath. The actual temperature of the red blood cell/Rejuvesol® Solution mixture does not reach 37 °C (the final temperature is usually 29-31 °C).

1. Place the primary collection bag containing the red blood cell/Rejuvesol® Solution mixture with the attached transfer bag of the Y-type Rejuvenation Set in a plastic overwrap bag and flatten the overwrap to remove all air prior to sealing.
2. Seal the plastic overwrap with tape or heat seal.
3. Place the sealed overwrapped unit inside a second overwrap bag containing lead weights (to keep the unit submerged during incubation); flatten and seal.
4. Place the overwrapped unit in the water bath and secure the overwrap to the inside wall of the water bath with waterproof tape.
5. Incubate the unit in a 37 °C water bath for 60 minutes with agitation.
6. Remove the overwrapped unit from the water bath; dry the outer overwrap with clean, disposable toweling and carefully remove the overwraps from the red blood cell/Rejuvesol® Solution mixture assuring that the primary collection bag and mixture are not contaminated with any water from the water bath.

III. TO PROCESS THE RED BLOOD CELL/Rejuvesol® Solution MIXTURE AFTER INCUBATION1,9,11,13

Complete the glycerolization procedure per Standard Operating Procedure. 1,10,11

NOTES:

i. After incubation, the red blood cell/Rejuvesol® Solution mixture may need to be concentrated prior to the addition of glycerol solution to insure proper glycerolization.1,9,11,13 ii. No more than four (4) hours should elapse between the time the unit is removed from the refrigerator and the time the cells are placed in the freezer.11

Rejuvesol
red blood cell processing solution

PN 7012 - 50 mL Vial Qty: 12

CitraLabs
A Biomet Biologics Company

Fragile: Handle with care.
Protect from freezing
Store Between 15°C - 25°C (59°F - 77°F)

Manufactured for:
Citra Labs, LLC
55 Messina Drive
Braintree, MA 02184
Phone: 1-800-299-3411
Fax: 781-848-6781

Manufactured by:
Grand River Aseptic Manufacturing
140 Front Ave SW Suite 3
Grand Rapids, MI 49504, USA

STERILE
15°C - 25°C

LA7012B
02/15

LOT X-XX-XXXX
EXP DATE YYYY/MM

Rejuvesol  sodium pyruvate, inosine, adenine, sodium phosphate, dibasic, and sodium phosphate, monobasic, monohydrate solution

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:23731-7000 Route of Administration EXTRACORPOREAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Sodium Pyruvate (Pyruvic Acid) Sodium Pyruvate 0.55 g  in 50 mL Inosine (Inosine) Inosine 1.34 g  in 50 mL Adenine (Adenine) Adenine 0.034 g  in 50 mL Sodium Phosphate, Dibasic (Phosphate Ion and Sodium Cation) Sodium Phosphate, Dibasic 0.73 g  in 50 mL Sodium Phosphate, Monobasic, Monohydrate (Phosphate Ion and Sodium Cation) Sodium Phosphate, Monobasic, Monohydrate 0.311 g  in 50 mL

Packaging # Item Code Package Description 1 NDC:23731-7000-5 12 VIAL, SINGLE-USE in 1 CASE 1 50 mL in 1 VIAL, SINGLE-USE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA BN950522 02/26/1997

Labeler - Citra Labs LLC (962863838)

Revised: 03/2016   Citra Labs LLC